A group of transforming growth factors (TGF's) have been identified in both normal and transformed cells from a variety of tissue types. These factors, which are effectors of malignant phenotypic transformation, are peptides closely associated with epidermal growth factor (EGF). EGF enhances the activity of some TGF's, (TGF-beta) while others bind to the EGF receptor. This study aims to define structure-function relationships of EGF and, ultimately, TGF molecules through synthetic and chemical modification techniques, leading primarily to the rational design of effective inhibitors. Our continuing work with EGF has led to identification of a localized region in which the information for receptor binding and early biological responses resides. In the past year, TGF-beta from three tissue types in two species (bovine and human) have been purified, and the amino acid composition and partial sequence have been determined using picomole quantities of material. Synthesis of peptide fragments have begun, and efforts to raise antibodies to specific regions of the molecule are underway.